Harden topped 20 points for the seventh straight game to send the 76ers to their fifth straight loss. He made 17 of 18 free throws, including six in the fourth quarter, as Houston improved to 9-2 in its last 11 home games.
Toney Douglas heated up in the fourth quarter for the Rockets, hitting five 3-pointers and scoring all 17 of his points.
Reserve Nick Young scored 21 points to lead Philadelphia, which matched its most lopsided loss of the season. The 76ers also lost by 22 points against the New York Knicks on Nov. 5.
Young hit a 3-pointer with less than three minutes left in the third quarter to cut Houston's lead to three, but the Rockets finished the quarter on an 8-1 run and led by 10 at the start of the fourth. Houston forward Greg Smith keyed the rally, scoring eight of his 13 points in the final two minutes of the third quarter.
Chandler Parsons got the rebound on his own 3-point attempt and followed with a powerful dunk that kept Houston's lead in double digits midway through the fourth quarter. Parson finished with nine points and was the only Rockets starter not in double-figures.
Jeremy Lin had 18 points and six assists, and Omer Asik added 17 points and 15 rebounds for Houston, which led by as many as 14 in the first half and was ahead 56-51 at the break.
Dorell Wright scored 20 points in a reserve role for Philadelphia, and Thaddeus Young added 17.
Philadelphia guard Evan Turner left the game with nine minutes left in the third quarter after suffering a left ankle injury. Turner limped to the locker room and returned with less than five minutes remaining, but he only stayed in the game for 17 seconds before heading back to the locker room.
Turner never re-entered the game and finished with six points, three assists and two rebounds, ending a 17-game streak of scoring in double-figures. The 2010 second overall pick has averaged 17.7 points in December and 15.5 this season.
Turner's absence might be the latest setback for the injury-plagued 76ers, who have been without center Andrew Bynum for the entire season.
Philadelphia point guard Jrue Holiday, the team's leading scorer at nearly 19 points per game, missed his fourth straight with a sprained left foot. Philadelphia coach Doug Collins said he hoped Holiday would be back for Friday's home game against Atlanta but said the team isn't rushing his return.
Notes: Texas A&M quarterback and Heisman Trophy winner Johnny Manziel attended the game and received a brief ovation when his name was announced halfway through the third quarter. Texas A&M University in College Station is roughly 100 miles from Houston's Toyota Center. ... Houston F Patrick Patterson missed his third straight game with a bone bruise in his right foot.